Peter A. LeWitt, MDHenry Ford Health System, Michigan

Readers may be surprised to learn that a placebo - a "sugar pill" containing no drug content can teach us a lot about Parkinson's disease (PD). Placebos mainly are used in medical research, commonly serving as tools for sorting out what a drug does and what its human recipient might expect it to accomplish. Their intent is not to be deceptive but, rather, to control for an inevitable part of the human experience: feeling better by taking a pill, no matter what its contents are. The placebo effect is a very real perception that a medication is helping, whether or not that pill actually has any pharmacological activity.

What are we learning about the Placebo Effect?

As recent science has shown, the placebo effect can be more than just an ill person's wishful thinking or positive attitude. Studies carried out in Parkinson's disease (PD) have provided fascinating insights into the placebo effect and has emphasized this phenomenon's importance in clinical research. There's experimental evidence that taking a placebo leads to changes in the brain, not unlike taking a dose of levodopa (the active ingredient of Sinemet). These investigations have used a research tool called positron emission tomography, which images the chemistry of the brain. Scientists at the University of British Columbia have shown that a placebo can enhance the signaling between nerve cells with dopamine, the brain chemical specifically deficient in PD. How is somewhat of a mystery, but the implication is clear - expecting an improvement from taking a pill thought to be therapeutic can exert a very real effect on the brain and PD symptoms. In some clinical trials, the degree of improvement on standard PD rating scales can be 20 percent or more. Any medication that has real promise needs to do much better.

Placebo effects are well-known to be active in other realms of brain function. For example, research into mechanisms of pain control also has emphasized that relief of 20 percent or more can occur just on the basis of expectation. Studies of depression, cognitive impairment, and of sleeping pills and many other medications, have also shown that, in proven therapies, there also may be some placebo effect. Many investigations of placebo effect have charted it as a changing response over time. In some clinical studies, the effect is most robust in the first few weeks after starting an experimental medication and gradually wanes thereafter. It has been demonstrable for three months or longer in some studies. Curiously, studies have detailed different magnitude and time course of placebo effects when examined in diverse populations participating in the same clinical trial. It should be obvious why using placebos in clinical research is so important. Any study judging the effectiveness of a new medication could yield misleading information if comparison to a placebo is not available.

Evaluating the Impact on Treatment

While modern medicines offer far more than placebo effect, both physician and patient should keep this in mind when evaluating the impact of treatments. Is that new (and expensive) medication really helping, or is just providing the perception of benefit? How long should a drug trial continue before reaching a conclusion as to whether it should be continued? Are there more objective ways to gauge the usefulness of a drug than just a "gut impression"? These questions can be challenging in everyday experiences of using PD medications. Fortunately, it is always possible to start and stop (and re-start) medications to discover what really works. As PD patients commonly experience fluctuations from dose to dose of medications with "good days and bad days," recognizing placebo effects may not be easy. Factors such as mood, anxiety, a restful night's sleep and distractions of a busy day al may modulate the perception of medication effect. So, the often-disparaged placebo effect may be just part of the bargain for the complexity of a human mind. Al¬though it can be confusing and adds to the cost of drug research for better PD drugs, the placebo effect is here to stay.